Lesions Produced with Sulfadiazine.

Changes apparently due to the sulfonamides have been reported in man and in experimental animals by several investigators. Some of the changes observed by us have not been hitherto described. Eight dogs, weighing from 8.2 to 16.4 kg, were used. In a 20% aqueous solution, one-tenth g of sodium sulfadiazine per kg of animal weight was injected subcutaneously twice daily. Tissues were examined from 6 to 21 days after the initial dose of this drug During the first 6 days blood levels were from 10 to 25 mg %; higher levels (up to 100 mg %) were found after the second week. All animals developed high values for blood urea nitrogen, became listless, and 6 died within 21 days. The 2 which remained were killed. A moderate bronchopneumonia was found in 2 animals. There were no other gross changes except for the presence of crystalline deposits in the pelves and calyces of all animals. The most striking changes in all experimental animals were found in the kidneys. This drug apparently affects several renal structures at approximately the same time. The lesions indicated below were present after 6 days, and with increased time the characteristics became more obvious. A moderate number of glomeruli were damaged. The first evidence of damage was the presence of protein and blood elements in Bowman's space and the urine. Later, inflammatory changes were encountered resulting in the destruction of the glomeruli. The leukocytic reaction consisted of monocytes, plasma cells, lymphocytes and a few polymorphonuclear neutrophils and eosinophils. This reaction was accompanied by the development of fibroblasts, collagen deposition and multinucleated giant cells producing a granuloma.